Nausea and Vomiting of Pregnancy and its Management with the Dual-Release Formulation of Doxylamine and Pyridoxine.

Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (T max ) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αß T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.

Female physician and pregnancy- effect of the amended German maternity protection act on female doctors' careers.

Objectives: In Germany, the 2018 amended Maternity Protection Act frequently leads to fundamental restrictions for female physicians, especially surgeons, and now even also for students impeding the progress of their careers. Our goal was to assess the current situation for pregnant female physicians and students, respectively, and their perspective on this amendment regarding their career path. Methods: A nationwide survey was conducted in Germany from December 2020 to February 2021. The questionnaire included 790 female physicians and students who were pregnant after the inception of the amended Act. Those women pregnant after the beginning of the corona pandemic were excluded. Results: The survey revealed that two thirds of female physicians worked a maximum of 50% in their previous professional activity as soon as they reported pregnancy. Amongst medical students this amounted up to 72%. 18% of the female physicians and 17% of the female medical students respectively could not follow the sense of these restrictions. 44% of female medical physicians and 33% of female students felt their career impeded. This led up to 43% amongst female medical doctors and 53% amongst female medical students, respectively, who were concerned to announce their pregnancy. As a consequence, pregnancies were reported at 12 weeks in female physicians compared to 19 weeks in medical students. Conclusions: Analyses of the current survey revealed that a relevant number of female physicians and medical students felt impeded in their career path through the application of the amended Maternity Act.

HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients.

BACKGROUND: To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. METHODS: This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). RESULTS: Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity. CONCLUSIONS: ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming.

Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.

Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia.

The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations and the underlying stromal compartment of endo- and ectocervix, encompassing the transition zone. Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodelling and increases expression of the Wnt inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Our data indicate that homeostasis at the transition zone results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages.

Stable expansion of high-grade serous ovarian cancer organoids requires a low-Wnt environment.

High-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium. Here, we established 15 organoid lines from HGSOC primary tumor deposits that closely match the mutational profile and phenotype of the parental tumor. We found that Wnt pathway activation leads to growth arrest of these cancer organoids. Moreover, active BMP signaling is almost always required for the generation of HGSOC organoids, while healthy fallopian tube organoids depend on BMP suppression by Noggin. Fallopian tube organoids modified by stable shRNA knockdown of p53, PTEN, and retinoblastoma protein (RB) also require a low-Wnt environment for long-term growth, while fallopian tube organoid medium triggers growth arrest. Thus, early changes in the stem cell niche environment are needed to support outgrowth of these genetically altered cells. Indeed, comparative analysis of gene expression pattern and phenotypes of normal vs. loss-of-function organoids confirmed that depletion of tumor suppressors triggers changes in the regulation of stemness and differentiation.

Chronic Chlamydia infection in human organoids increases stemness and promotes age-dependent CpG methylation.

Chronic infections of the fallopian tubes with Chlamydia trachomatis (Ctr) cause scarring and can lead to infertility. Here we use human fallopian tube organoids and genital Ctr serovars D, K and E for long-term in vitro analysis. The epithelial monolayer responds with active expulsion of the bacteria into the lumen and with compensatory cellular proliferation-demonstrating a role of epithelial homeostasis in the defense against this pathogen. In addition, Ctr infection activates LIF signaling, which we find to be an essential regulator of stemness in the organoids. Infected organoids exhibit a less differentiated phenotype with higher stemness potential, as confirmed by increased organoid forming efficiency. Moreover, Ctr increases hypermethylation of DNA, which is an indicator of accelerated molecular aging. Thus, the chronic organoid infection model suggests that Ctr has a long-term impact on the epithelium. These heritable changes might be a contributing factor in the development of tubal pathologies, including the initiation of high grade serous ovarian cancer.

Follow-up after radical vaginal trachelectomy (RVT): patients' problems and physicians' difficulties.

PURPOSE: Patients after radical vaginal trachelectomy (RVT) need specific follow-up treatment because their problems differ from those of other gyneco-oncologic patients. Anatomic changes after surgery complicate examinations. Recognition and treatment of these issues require physician's expertise. PATIENTS AND METHODS: We evaluated the follow-up data of 70 patients who underwent RVT for early cervical cancer between 03/2010 and 12/2013. The follow-up interval in the first 2 years was 3 and 6 months in the following 2 years. We used a tailored protocol to describe the special problems after RVT. RESULTS: Cervical stenosis was one of the central problems independent of time interval to RVT. Physicians' most significant problem was to locate the exact position of the neo-cervix and thus to receive valid pap smears. CONCLUSIONS: Follow-up of patients after RVT needs special expertise because the symptoms differ from those after hysterectomy and examinations ensuring oncologic safety require special attention.

Closure of the cervical os in patients after fertility preserving treatment for early cervical cancer - results of a prospective observational study.

INTRODUCTION: Up to 50% of the infants delivered after radical vaginal trachelectomy (RVT) are born prematurely. An effective strategy to reduce this number could be the closure of the cervical os (CCO). PATIENTS AND METHODS: Fifteen pregnant patients who had a RVT due to early cervical cancer were included in this prospective case control study. All patients were scheduled for CCO early in the second trimester. CCO was performed in 12 patients. Their data were compared to data from 125 pregnancies after a RVT without CCO. RESULTS: The patients who had CCO were compared to patients without CCO. One patient had an early rupture of the amniotic membranes prior to CCO. Two patients chose not to undergo CCO. In 12 patients CCO was performed without complications. There was no early preterm delivery in the CCO group as compared to a rate of 5% in 125 pregnancies in the non-CCO group. DISCUSSION: We developed a protocol to reduce the risk of preterm deliveries after a RVT. Digital examinations should be avoided. Vaginal checks for pH can discover ascending infections - the main cause of preterm deliveries after a RVT. Infections should be treated adequately. CCO can further reduce the risk of preterm deliveries after a RVT.

The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids.

The epithelial lining of the fallopian tube is of critical importance for human reproduction and has been implicated as a site of origin of high-grade serous ovarian cancer. Here we report on the establishment of long-term, stable 3D organoid cultures from human fallopian tubes, indicative of the presence of adult stem cells. We show that single epithelial stem cells in vitro can give rise to differentiated organoids containing ciliated and secretory cells. Continuous growth and differentiation of organoids depend on both Wnt and Notch paracrine signalling. Microarray analysis reveals that inhibition of Notch signalling causes downregulation of stem cell-associated genes in parallel with decreased proliferation and increased numbers of ciliated cells and that organoids also respond to oestradiol and progesterone treatment in a physiological manner. Thus, our organoid model provides a much-needed basis for future investigations of signalling routes involved in health and disease of the fallopian tube.

European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients.

Endometrial cancer (EC) in young women of reproductive age is a relatively rare diagnosis. However, since in the modern era women delay their childbearing for a variety of social reasons, more and more women in the near future will be nulliparous and have a diagnosis of EC at the same time. Hence, a more conservative approach of EC is desirable to preserve fertility of these women, without compromising their survival. Recently, the number of studies reporting encouraging results on fertility-sparing management of EC with high dose of progestins is increasing. It seems that preserving the uterus and the ovaries in a carefully selected patient with EC confers only a very small risk combined with an enormous benefit. Selection of women suitable for such a conservative approach, as well as method of treatment, follow-up, recurrence, obstetric outcomes, and survival rates are very important parameters when consulting women with EC wishing to preserve their fertility. In this article, we try to elucidate all the previously mentioned aspects and formulate clinical recommendations, based on published data, about the most proper approach and consultation of these patients.

The efficacy of short-term psycho-oncological interventions for women with gynaecological cancer: a randomized study.

OBJECTIVES: We aimed to examine the efficacy of two psycho-oncological interventions in anxiety, depression, and self-perceived as well as physiological stress in inpatients with gynaecological cancer. METHODS: Forty-five women were included in the trial. Thirty-five were categorized as being at high risk of anxiety and depression, and were randomized to either a single psycho-oncological therapy session or a single-session relaxation intervention. RESULTS: A significant decrease in anxiety [mean (t0) = 12, mean (t1) = 7.47, p = 0.001] and depression [mean (t0) = 9.71, mean (t1) = 6.35, p < 0.001] was observed in the psycho-oncological intervention group. In the relaxation group, anxiety also significantly decreased [mean (t0) = 11.67, mean (t1) = 8.22, p = 0.003], whereas depression did not. A comparative analysis of both interventions showed a trend in favour of psycho-oncological therapy for the treatment of depression (F = 3.3, p = 0.078). However, self-reported stress (p = 0.031) and different objective stress parameters only significantly decreased in the relaxation group. CONCLUSIONS: Psycho-oncological interventions should represent an essential part of interdisciplinary care for gynaecological cancer patients. Both types of intervention may reduce anxiety. However, the single psycho-oncological therapy session might be slightly more effective in treating depression, whereas the single-session relaxation intervention seems to have a stronger effect on physiological stress parameters.

Long-term follow-up and recurrence rate after mesorectum-sparing bowel resection among women with rectovaginal endometriosis.

OBJECTIVE: To demonstrate the quality of a combined vaginal-abdominal surgical approach to rectovaginal endometriosis by analyzing long-term outcome and recurrence rates. METHODS: In a prospective cohort study in Berlin, Germany, women with endometriosis of the rectovaginal septum were enrolled between September 2004 and December 2012. Bowel infiltration was verified intraoperatively and treated by a nerve-sparing, mesentery-preserving vaginal-abdominal operative approach. Operative results were evaluated by assessing short- and long-term complications and recurrence rates. RESULTS: During the study period, 110 women underwent surgery. For 71 (64.5%) patients, bowel infiltration was confirmed intraoperatively. Overall, 15% of the patients had peri- or postoperative complications. No long-term complications occurred. After a median follow-up of 64 months, no recurrence in the rectovaginal septum was observed among the study patients. The recurrence of pelvic endometriosis was 15%. CONCLUSION: The surgical nerve-sparing approach to rectovaginal endometriosis was confirmed to facilitate precise diagnosis and treatment with minimal morbidity and a long-term complication rate of 0%.

Radical vaginal trachelectomy after laparoscopic staging and neoadjuvant chemotherapy in women with early-stage cervical cancer over 2 cm: oncologic, fertility, and neonatal outcome in a series of 20 patients.

OBJECTIVES: The aim of the study was to assess oncologic and fertility outcome of treatment in patients with cervical cancer of more than 2 cm seeking parenthood. METHODS: The regimen consisted of laparoscopic lymphadenectomy as a staging procedure to confirm no lymph node metastases before neoadjuvant chemotherapy (NACT) consisting of 2 or 3 cycles of paclitaxel/ifosfamide/cisplatin followed by radical vaginal trachelectomy (RVT). Oncologic and fertility outcome was evaluated prospectively. RESULTS: Twenty women were enrolled up to now. The mean age was 32 years (range, 26-41 years), and mean tumor size was 3 cm (range, 2.1-5.0 cm). Lymphadenectomy was performed before NACT without complications. During NACT, hematologic toxicity grade 3 was observed in 2 of 20 patients, and renal toxicity grade 3 in 1 of 20 patients. Radical vaginal trachelectomy was performed in 18 women until now with 2 intraoperative complications (ureter injury and injury of internal iliac vein). There were no severe postoperative or long-term complications. Complete pathologic remission was found in 9 of 18 patients. In 2 of 18 patients, chemoradiation was recommended because of insufficient pathologic response in the RVT specimen. After a mean follow-up of 23 months (range, 1-88 months), 1 relapse was observed. After RVT, 7 women tried to conceive until now. Seven pregnancies occurred in 5 women. Four children were born, 2 of whom were premature (31 weeks 2 days and 33 weeks 4 days of gestation); 1 pregnancy is ongoing. CONCLUSIONS: Laparoscopic lymphadenectomy followed by NACT and RVT in pN0 patients with cervical cancer of more than 2 cm seems to be an oncologically safe procedure with promising fertility outcomes.

Laparoscopic pelvic lymphadenectomy in 32 pregnant patients with cervical cancer: rationale, description of the technique, and outcome.

OBJECTIVE: Individualized treatment of pregnant patients with cervical cancer is mandatory; hence, information on nodal status is pivotal to allow a waiting strategy in early-stage disease.We aimed to verify the oncological safety and surgical reproducibility of a standardized laparoscopic pelvic lymphadenectomy in pregnant patients with cervical cancer. METHODS: We standardized laparoscopic pelvic lymphadenectomy during the first and second term of gestation in 32 patients with cervical cancer since 1999. According to gestational week (GW) of less than 16 GWs or more than 16 GWs, 2 different techniques were used. RESULTS: The International Federation of Gynecology and Obstetrics stages were IA in 10 patients, IB1 in 17 patients, IB2 in 4 patients, and IIA in 1 patient. Mean (SD) GW was 17.5 (5.1) weeks. Mean (SD) operative time was 105.4 (29) minutes. Mean (SD) blood loss was 5.3 (10.2) mL. There were no conversion to laparotomy and no intraoperative complications. A median number of 14 pelvic lymph nodes (range, 8-57) were harvested. Median hospital stay was 6 days. Median follow-up is 42.5 months (range, 17-164). Four patients had lymph node metastases. Five patients interrupted their pregnancy. Fourteen patients were given neoadjuvant platin-based systemic therapy. All patients are alive and disease free. All children born through cesarean delivery at a mean (SD) 34 (1.9) GWs are well and show normal clinical neurological development. CONCLUSIONS: To the best of our knowledge, this is the largest series so far reported on laparoscopic pelvic lymphadenectomy during pregnancy. This procedure is safe and associated with good oncological and obstetrical outcomes.

Isthmic-vaginal smear cytology in the follow-up after radical vaginal trachelectomy for early stage cervical cancer: is it safe?

BACKGROUND: Isthmic-vaginal cytology is a follow-up method in patients who have undergone radical vaginal trachelectomy (RVT) for early cervical cancer. However, to the authors' knowledge, little is known regarding its ability to monitor patients and diagnose disease recurrence. Herein, the authors report their experience with cytology after RVT compared with cytology in patients after cone biopsy and women undergoing screening. METHODS: A database of 563 specimens from 303 patients was analyzed retrospectively (RVT in 361 specimens, conization in 102 specimens, and screening in 100 specimens). The following criteria were applied: Bethesda system, the presence of endocervical and metaplasia cells, regeneration criteria, vaginal flora, and morphological signs of human papillomavirus. The analysis was performed by 2 cytopathologists. Differences between the groups and correlation between the cytopathologists were analyzed. RESULTS: Smears without endocervical and metaplasia cells were significantly less frequent among the patients who underwent RVT. There was no difference in regeneration signs, vaginal flora, and morphologic signs of human papillomavirus between the groups. After RVT, 26/23 smears (cytopathologist 1/cytopathologist 2) smears were diagnosed as abnormal. Biopsies revealed 7 cases of dysplasia and 1 case of disease recurrence. After conization, 1 patient was diagnosed with a low-grade lesion on cytology; follow-up cytology was normal. In the screening, 10/13 smears were diagnosed with lesions on cytology; biopsy revealed dysplasia in 2 cases. The correlation between both cytopathologists was high. CONCLUSIONS: After RVT, histological verification of cytology is frequently needed. The reasons might include alterations of anatomy, regeneration, and inflammation process after RVT. Cytopathologists should become familiar with the spectrum of changes in post-RVT cytology and communication between cytopathologists and clinicians should be improved. This might reduce false-positive results.

Vaginal-assisted laparoscopic radical hysterectomy (VALRH) versus laparoscopic-assisted radical vaginal hysterectomy (LARVH) in the treatment of cervical cancer: surgical results and oncologic outcome.

PURPOSE: The aim of this study was to compare the morbidity and survival rates of patients with early-stage cervical cancer treated by vaginal-assisted laparoscopic radical hysterectomy (VALRH) with pair-matched laparoscopic-assisted vaginal radical hysterectomy (LARVH) controls. METHODS: One hundred nine patients who underwent VALRH for cervical cancer stage FIGO Ia1, L1 to IIb between 2007 and 2009 and 200 patients who underwent LARVH between 1994 and 2002 were analysed in their entirety and in a group of matched pairs. RESULTS: In both groups, there was no conversion to laparotomy due to an intraoperative complication. Prevalence of blood transfusions was significantly lower in the VALRH group (2 vs. 39 patients; P < 0.001). Bladder function resumed sooner (P < 0.001), and patients were discharged earlier after VALRH (P < 0.001). There were no intraoperative injuries in the VALRH group. In the LARVH group, the most common intraoperative injury occurred to the bladder (7.0 %). Postoperatively, the most common complication in the VALRH group was ureterovaginal fistula (2.7 %) and fever (2.7 %) and in the LARVH ureterostenosis (3.5 %), uretero/bladder fistula (1 %), and fever (7 %). For patients with tumour stage Ib1 the 5-year recurrence-free survival was 92.8 % and 5-year overall survival 95.2 % following VALRH and 88.2 and 90.5 %, respectively, following LARVH. No significant difference in the survival rate was found (log rank, P = 0.740). CONCLUSION: VALRH is a feasible and oncologically safe surgical option for patients with early-stage cervical cancer. We believe the complication rate is lowered in VALRH by the combination of the laparoscopic and vaginal approach.

Pattern of cancer recurrence in 320 patients after radical vaginal trachelectomy.

OBJECTIVE: The oncological outcome regarding disease-free survival and overall survival after radical vaginal trachelectomy (RVT) is the same as the rates after radical hysterectomy. We aim to analyze predictive and risk factors and death in patients with cervical cancer undergoing fertility preservation by laparoscopic lymphadenectomy and RVT. METHODS: Three hundred twenty patients with cervical cancer underwent RVT between March 1995 and February 2013. In our study, we examined recurrence rates analyzed by risk factors. We classified the presence of lymphovascular space invasion, depth of tumor infiltration, tumor size, and tumor grading as risk factors. The mean follow-up time was 48 months. RESULTS: Ten of the 320 patients had cancer recurrence. Recurrence appeared at a mean time of 26.1 months (3-108 months) after RVT. Five patients died within 8.8 months (4-15 months) after recurrence was diagnosed. Two of these 5 patients had distant metastasis at the time of recurrence. Five patients were treated successfully by surgery, and 4 patients were treated successfully by chemotherapy. The mean follow-up after the recurrence of these 5 patients is 76 months (6-120 months). None of the 10 patients with recurrences in our series showed significant high-risk factors. CONCLUSION: There seems to be no pattern in the recurrence of cancer after RVT. It is strictly mandatory to follow up the patients closely every 3 months after RVT to diagnose recurrence at an early stage so therapeutic options such as chemoradiation are still available. Once distant metastasis occurs, prognosis is not good.

Seroprevalence of anti-N-methyl-D-aspartate receptor antibodies in women with ovarian teratoma.

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.